An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease

NCT02262728 | Completed Phase 2 Results DMC

• 2 other identifiers: CR105028TMC435HPC2010
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the efficacy of a 12-week regimen containing simeprevir, daclatasvir and sofosbuvir in participants with decompensated liver disease (the liver function is insufficient) due to genotype 1 or 4 Hepatitis (inflammation of the liver) C virus (HCV) infection by assessing sustained virologic response 12-weeks after the end of study drug treatment (SVR12).

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C, Chronic; Simeprevir; Daclatasvir; Sofosbuvir; Decompensated Liver Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)

  Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the end of study drug treatment.

  Week 24

Secondary Outcomes (12)

• Percentage of Participants With On-Treatment Virologic Response

  Week 1, 2, 4, 6, 8, 10, 12

• Percentage of Participants With SVR 4 Weeks After End of Study Drug Treatment (SVR4) and SVR 24 Weeks After End of Study Drug Treatment (SVR24)

  Week 16 and Week 36

• Percentage of Participants With HCV NS3/4A Sequence, NS5A and NS5B After End of Treatment in Participants Not Achieving SVR

  Baseline, Day 3, Week 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, and Year 1, 1.5, 2, 2.5, 3 after end of treatment

• Absolute Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels at Follow-up Week 24 (Week 36)

  Follow-up Week 24 (Week 36)

• Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir, Daclatasvir, Sofosbuvir and GS-331007 (Sofosbuvir Metabolite)

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose on Weeks 2 and 8

Study Arms (2)

Panel 1

EXPERIMENTAL

Participants with Child-Pugh score \<7 with evidence of portal hypertension (confirmed by presence of esophageal varices or hepatic venous pressure gradient \[HVPG\] greater than or equal to 10 millimeter of mercury \[mm Hg\]) will receive simeprevir (150 milligram \[mg\] capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.

Drug: Simeprevir; Drug: Daclatasvir; Drug: Sofosbuvir

Panel 2

EXPERIMENTAL

Participants with Child-Pugh score 7 to 9 (extremes included) will receive simeprevir (150 mg capsule), daclatasvir (60 mg tablet) and sofosbuvir (400 mg tablet) orally once daily for 12 weeks.

Drug: Simeprevir; Drug: Daclatasvir; Drug: Sofosbuvir

Interventions

Simeprevir DRUG

Simeprevir 150 milligram (mg) capsule orally once daily for 12 weeks

Also known as: TMC435

Panel 1; Panel 2

Daclatasvir DRUG

Daclatasvir 60 mg tablet orally once daily for 12 weeks

Also known as: BMS-790052

Panel 1; Panel 2

Sofosbuvir DRUG

Sofosbuvir 400 mg tablet orally once daily for 12 weeks

Also known as: GS-7977

Panel 1; Panel 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented chronic Hepatitis C virus (HCV) infection: diagnosis of HCV more than (\>) 6 months before the Screening visit, either by detectable HCV ribonucleic acid (RNA), a HCV positive antibody or the presence of histological changes consistent with chronic hepatitis
• HCV genotype 1 or 4 infection and HCV RNA plasma level \>10,000 international unit per milliliter (IU/mL) (both determined at screening)
• Presence of cirrhosis, which is defined as a FibroScan with a result of \>14.5 kilopascals (kPa) at Screening
• HCV treatment-naive participants: participant has not received treatment with any approved or investigational drug for the treatment of HCV infection and HCV treatment-experienced participants: participant has had at least 1 documented previous course of a non-direct-acting antiviral agent (DAA), interferon (IFN)-based HCV therapy (with or without Ribavirin \[RBV\]). Last dose in this previous course should have occurred at least 2 months prior to Screening
• Decompensated liver disease: Panel 1: Child Pugh A (mild hepatic impairment) with evidence of portal hypertension \[confirmed by the presence of esophageal varices on gastroscopy or hepatic venous pressure gradient (HVPG) greater than or equal to (\>=) 10 millimeter of mercury (mm Hg)\], Panel 2: Child-Pugh B (moderate hepatic impairment) 7 to 9 (extremes included)

You may not qualify if:

• Co-infection with any HCV genotype
• Co-infection with human immunodeficiency virus (HIV)-1 or -2 (positive HIV-1 or HIV-2 antibodies test at Screening)
• Co-infection with hepatitis B virus (hepatitis B surface antigen \[HBsAg\] positive)
• Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the Investigator
• Use of any disallowed therapies before the planned first dose of study drugs

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

San Antonio, Texas, United States

Location

Related Publications (2)

• Lawitz E, Poordad F, Gutierrez JA, Beumont M, Beets G, Vandevoorde A, Remoortere PV, Luo D, Vijgen L, Eygen VV, Gamil M. Simeprevir, daclatasvir, and sofosbuvir for hepatitis C virus-infected patients: Long-term follow-up results from the open-label, Phase II IMPACT study. Health Sci Rep. 2020 Feb 22;3(2):e145. doi: 10.1002/hsr2.145. eCollection 2020 Jun.

  PMID: 32270053 DERIVED

• Lawitz E, Poordad F, Gutierrez JA, Kakuda TN, Picchio G, Beets G, Vandevoorde A, Van Remoortere P, Jacquemyn B, Luo D, Ouwerkerk-Mahadevan S, Vijgen L, Van Eygen V, Beumont M. Simeprevir, daclatasvir and sofosbuvir for hepatitis C virus-infected patients with decompensated liver disease. J Viral Hepat. 2017 Apr;24(4):287-294. doi: 10.1111/jvh.12645. Epub 2016 Nov 23.

  PMID: 27878906 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Simeprevir; daclatasvir; Sofosbuvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Medical Leader Hepatitis C, GCO ED&CP
• Organization: Janssen Research & Development, a division of Janssen Pharmaceutica NV

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 13, 2014
• Study Start: September 30, 2014
• Primary Completion: August 13, 2015
• Study Completion: April 25, 2018
• Last Updated: February 4, 2025
• Results First Posted: February 13, 2017

Record last verified: 2025-01

Locations

US (1)